The detection and treatment of cancerous tissue has been the subject of intense investigation for many years. One among the many approaches to its detection has concerned the identification of tumor specific antigens. Where these antigens can be identified, radionucleid labeled antibodies have been employed which tend to collect at tumor sites. When concentrated, somewhat elaborate radiation detection equipment then is employed to record, for example, by imaging the concentrations of the emissive substances and thus to locate neoplastic tissue. Important advances in this procedure have been evidenced through the use of monoclonal antibodies or fragments thereof with a variety of radionucleides. Typical techniques for carrying out imaging of these antibodies have involved, for example, tomographic scanning, immunoscintigraphy and the like. The particular choice of radionucleid for labeling antibodies is dependent upon its nuclear properties, the physical half life, the detection instrument capabilities, the pharmacokinetics of the radiolabeled antibody, and the degree of difficulty of the labeling procedure. The most widely used of these radionucleides in nuclear medicine imaging include technetium, .sup.99m Tc, iodine .sup.125 I, .sup.131 I, and indium, .sup.111 In. Of the above, for localizing tumors of the gastro-intestinal tract, the radionucleid .sup. 131 I is used as the marker or label in conjunction with imaging gamma cameras and the like which are relatively large and elaborate devices positioned above the patient during the imaging process.
In spite of its somewhat extensive utilization, .sup.131 I is not an ideal radionucleid for use in diagnostic medicine. The high energy gamma-photon emitted from .sup.131 I is poorly detected by the classic gamma camera and like instrumentation. In addition, the administered marker emissions deliver a high radiation dose to the patient. Further, the imaging definition of these external imaging devices has not been satisfactory for many reasons. As tumor sites become smaller, the radionucleid concentrations thereat will tend to be lost, from an imaging standpoint, in the background or blood pool radiation necessarily present in the patient.
Over the recent past, a surgical procedure has been developed concerning the differentiation and removal of such neoplastic tissue through the use of much lower energy gamma emission levels, for example, .sup.125 I (27-35 kev). While such radiolabel cannot be employed with conventional external imaging or scanning devices because the radiation is strongly absorbed by the tissue intermediate between the tumor and the surface of the patient's body, it has been found that when employed with a probe type detection structure, a highly effective differentiation technique can be evolved. More particularly, the longer half life of this type of radiolabel coupled with a surgical methodology involving the waiting of appropriate intervals from the time of introduction of the radiolabeled antibody to the patient to the time of surgery, can evolve a highly accurate differentiation of cancerous tumor. This improved method of localization, differentiation, and removal of cancerous tumor involves a surgical procedure wherein the patient suspected of containing neoplastic tissue is administered an effective amount of an antibody specific for neoplastic tissue which is labeled with a radioactive isotope as above-noted exhibiting photon emissions of specific energy levels. Next, the surgical procedure is delayed for a time interval following such administration for permitting the labeled antibody to preferentially concentrate in any neoplastic tissue present in the patient, as well as to be cleared from normal tissue so as to increase the ratio of photon emissions from the neoplastic tissue to the background photon emissions. Thereafter, an operative field to be examined for neoplastic tissue has the background photon emission count determined. Once the background photon emission count for the tissue within the operative field has been determined, this handheld probe is manually positioned within the operative field adjacent tissue suspected of being neoplastic. Readouts then can be achieved from probe counting for differentiation. In the above regard, reference is made to the following technical publications:
I. "CEA-Directed Second-Look Surgery in the Asymptomatic Patient after Primary Resection of Colorectal Carcinoma", E. W. Martin, Jr., MD, J. P. Minton, MD, PhD, Larry C. Carey, MD. Annals of Surgery 202:1 (September 1985 301-12). PA0 II. "Intraoperative Probe-Directed Immunodetection Using a Monoclonal Antibody", P. J. O'Dwyer, MD, C. M. Mojzsik, RN MS, G. H. Hinkle, RPh, MS, M. Rousseau, J. Olsen, MD, S. E. Tuttle, MD, R. F. Barth, PhD, M. O. Thurston, PhD, D. P. McCabe MD, W. B. Farrar, MD, E. W. Martin, Jr., MD. Archives of Surgery, 121 (December, 1986) 1321-1394. PA0 III. "Intraoperative Radioimmunodetection of Colorectal Tumors with a Hand-Held Radiation Detector", D. T. Martin, MD, G. H. Hinkle, MS RPh, S. Tuttle, MD, J. Olsen, MD, H. Abdel-Nabi, MD, D. Houchens, PhD, M. Thurston, PhD, E. W. Martin, Jr., MD. American Journal of Surgery, 150:6 (December, 1985) 672-75. PA0 IV. "Portable Gamma Probe for Radioimmune Localization of Experimental Colon Tumor Xenografts", D. R. Aitken, MD, M. O. Thurston, PhD, G. H. Hinkle, MS RPh, D. T. Martin, MD, D. E. Haagensen, Jr., MD, PhD, D. Houchens, PhD, S. E. Tuttle, MD, E. W. Martin, Jr., MD. Journal of Surgical Research, 36:5 (1984) 480-489. PA0 V. "Radioimmunoguided Surgery: Intraoperative Use of Monoclonal Antibody 17-1A in Colorectal Cancer". E. W. Martin, Jr., MD, S. E. Tuttle, MD, M. Rousseau, C. M. Mojzsik, RN MS, P. J. O'Dwyer, MD, G. H. Hinkle, MS RPh, E. A. Miller, R. A. Goodwin, O. A. Oredipe, MA, R. F. Barth, MD, J. O. Olsen, MD, D. Houchens, PhD, S. D. Jewell, MS, D. M. Bucci, MS, D. Adams, Z. Steplewski, M. O. Thurston, PhD, Hybridoma, 5 Suppl 1 (1986) S97-108.
Reference further is made to commonly assigned U.S. Pat. No. 4,782,840, entitled "Method for Locating, Differentiating, and Remove Neoplasms", by Edward W. Martin, Jr., and Marlin O. Thurston, issued Nov. 8, 1988.
The success of this highly effective differentiation and localization technique is predicated upon the availability of a probe-type detecting device capable of detecting extremely low amounts of radiation necessarily developed with the procedure. In this regard, low energy radionucleides are used such as .sup.125 I and the distribution of radiolabeled antibody with the nucleid is quite sparse so that background emissions can be minimized and the ratio of tumor-specific counts received to background counts can be maximized. Conventional radiation detection probe-type devices are ineffective for this purpose. Generally, because a detection device is required for the probes which is capable of performing at room temperatures, a very fragile or delicate detection crystal such as cadmium telluride is employed. The probe using such a crystal must be capable of detecting as little as a single gamma ray emission which may, for example, create electron-hole pairs in the crystal of between about 2,000 and 4,000 electrons. Considering that an ampere generates 6.25.times.10.sup.18 electrons per second, one may observe that extremely small currents must be detectable with such a probe. However, the probe system also must be capable of discriminating such currents from any of a wide variety of electrical disturbances, for example which may be occasioned from cosmic inputs, room temperature molecular generated noise, and capacitively or piezoelectrically induced noise developed from the mere manipulation of the probe itself. While being capable of performing under these extreme criteria, the same probe further must be capable of performing under the requirements of the surgical theater. In this regard, it must be secure from ingress of contaminants; it must be sterilizable; and it must be rugged enough to withstand manipulation by the surgeon within the operating room environment. Further, the system with which the probe is employed, must be capable of perceptively apprising the surgeon of when neoplastic tissue is being approached such that the device may be employed for the purpose of guiding the surgeon to the situs of cancer. Additionally, for surgical use, the probe instrument must be small, so as to be effectively manipulated through surgical openings and the like. Such dimunitive size is not easily achieved under the above operational criteria. This technique has been described as "radioimmuno-guided surgery", a surgical approach developed by E. W. Martin, Jr., MD, and M. O. Thurston, PhD.
In addition to the capability of performing under the above-noted relatively extreme criteria, the probe instrument called upon for the instant use should be fabricable employing practical manufacturing techniques. One approach to improving the fabricability of the probe instruments is described in U.S. Pat. No. 4,893,013, issued Jan. 9, 1990 entitled "Detector and Localizer for Low Energy Radiation Emissions" by Denen, et al. The probe structuring disclosed therein is one wherein necessary ground and bias are applied to opposite sides of the gamma detecting crystal utilizing electrodes which are fixed to the crystal face. An elastomeric retainer is used to structurally retain all the components together including the crystal, the biasing arrangement, and the like. While successful production has been achieved with the structure so described, the technique described therein is one requiring the use of a multi-component cap for the assembly and one wherein deterioration has been noted in the coupling of the bias and grounding electrodes to the radiation responsive crystals. Further improvements in the structure of the probe have been deemed necessary both in terms of the integrity of the association of external components with the gamma radiation crystal as well as in conjunction with the ease of fabricability of the probe.